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Ed Stannard, New Haven Register, Conn.
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Depression or depressive disorder is an illness that involves the body, mood, and thoughts. Depression is considered a mood disorder. Imbalances in three neurotransmitters (brain chemicals), including serotonin, norepinephrine, and dopamine, are linked to depression. Depression affects the way a person eats and sleeps, the way one feels about oneself, and the way one thinks about life situations. Unlike normal emotional experiences of sadness, loss, or passing mood states, depressive disorders are persistent and can significantly interfere with an individual's thoughts, behavior, mood, activity, and physical health.

According to the National Institute of Mental Health (NIMH), depressive disorders affect approximately 18.8 million American adults or about 9.5% of the U.S. population age 18 and older in a given year. This includes major depressive disorder (severe depression), dysthymic disorder (mild to moderate depression), and bipolar disorder (manic-depressive). Among all medical illnesses, major depression is the leading cause of disability in the U.S. and many other developed countries.

Without treatment, symptoms can last for weeks, months, or years. Appropriate treatment, however, can help most people who suffer from depression.

Children and teenagers can also suffer from depression. Depression in the young is defined as an illness when the feelings of depression persist and interfere with a child or adolescent's ability to function.

The American Academy of Child and Adolescent Psychiatry estimates that about 5% of children and adolescents in the general population suffer from depression at any given point in time. Children under stress, who experience loss, or who have trouble with attention, learning, conduct, or anxiety disorders are at a higher risk for depression.

Neurotransmitter imbalances: Studies suggest that a low or high level of neurotransmitters such as serotonin, norepinephrine, or dopamine cause depression. Studies have found evidence that a change in the sensitivity of the receptors on nerve cells to these neurotransmitters may be one issue, along with an imbalance in the amounts of neurotransmitters. Balancing neurotransmitters with drug therapy is the current focus for treatment of major depression.

Heredity: Researchers have identified several genes that may be involved in bipolar disorder and are looking for genes linked to other types of depression. But not everyone with a family history of depression develops the disorder, and conversely, people with no family history of the disorder can become depressed.

Gender: Depression occurs twice as frequently in women as in men, for reasons that are not fully understood. Hormonal changes such as menstrual cycle changes, postpartum period, pre-menopause, pregnancy, childbirth, miscarriage, and menopause are the most likely causes of depression.

Although men are less likely to suffer from depression than women, six million men in the United States are affected by the illness. Men are less likely to admit to depression. The rate of suicide in men is four times that of women, though more women attempt it.

Stress: Stressful life events, particularly a loss or threatened loss of a loved one or a job, can trigger depression.

Medications: Long-term use of certain medications, such as some drugs used to control high blood pressure, sleeping pills, or birth control pills, may cause symptoms of depression in some people.

Illnesses: Having a chronic illness, such as heart disease, stroke, diabetes, cancer or Alzheimer's disease, puts an individual at a higher risk of developing depression. Having an underactive thyroid (hypothyroidism), even mildly, also can cause depression. Physical trauma (damage) to the brain can also trigger depression.

Personality: Certain personality traits, such as having low self-esteem and being overly dependent, self-critical, pessimistic and easily overwhelmed by stress, can make an individual more vulnerable to depression.

Postpartum depression: It is common for mothers to feel a mild form of distress that usually occurs a few days to weeks after giving birth. During this time the woman may have feelings of sadness, anger, anxiety, irritability and incompetence. A more severe form of the baby blues, called postpartum depression, also can affect new mothers.

Hormones: Women experience depression about twice as much as men, which leads researchers to believe hormonal factors may play a role in the development of depression.

Alcohol, smoking, and drug abuse: Abuse of alcohol, cigarettes, and recreational drugs such as cocaine, methamphetamine (crystal meth), ecstasy, and marijuana can lead to depression.

Previous depression: More than half of those who experience a single episode of depression will continue to have episodes that occur as frequently as once or even twice a year. Without treatment, the frequency of depressive illness as well as the severity of symptoms tends to increase over time. Left untreated, depression can lead to suicide.

The onset of the first episode of depression may not be obvious if it is gradual or mild. The symptoms of depression represent a significant change from how a person functioned before the illness. Symptoms of depression can either be mild, moderate or severe.

Loss of interest in normal daily activities: An individual may lose interest in or pleasure from activities that they used to enjoy.

Depressed mood: The individual may feel sad, helpless or hopeless, and may have crying spells.

Sleep disturbances: Sleeping too much or having problems sleeping can be a sign of depression. Waking in the middle of the night or early in the morning and not being able to get back to sleep are typical.

Impaired thinking or concentration: The individual may have trouble concentrating, making decisions, or have problems with memory.

Weight changes: An increased or reduced appetite and unexplained weight gain or loss may indicate depression.

Fatigue (tiredness): Weariness and a lack of energy nearly every day are common signs of depression. The individual may feel as tired in the morning as they did when going to bed the night before.

Low self-esteem: Feelings of worthlessness and excessive guilt are common symptoms of depression.

Loss of sexual interests: If the individual was sexually active before developing depression, they may notice a dramatic decrease in the level of interest in having sexual relations.

Preoccupation with death: The individual may have a persistent negative view of their situation in life and the future. They may have thoughts of death, dying or suicide.

Other physical symptoms: Depression can also cause a wide variety of physical complaints, such as gastrointestinal problems (indigestion, constipation, or diarrhea), headache, and backache. Many people with depression also have symptoms of anxiety, including restlessness, inability to concentrate, and loss of sleep.

Depression in children and the elderly: Children, teens, and older adults may react differently to depression. In these groups, symptoms may take different forms or may be masked by other conditions. Kids may pretend to be sick, worry that a parent is going to die, perform poorly in school, refuse to go to school, or exhibit behavioral problems. The elderly may be more willing to discuss the physical symptoms of depression, instead of their emotional difficulties, including constant complaining about aches and pains.

Suicidal thoughts: Suicidal thoughts may accompany depression. Anyone who has suicidal feelings, talks about suicide, or attempts suicide should be taken seriously and should receive immediate help from a mental health specialist. Certain warning signs may indicate serious depression and the possibility of suicide. Danger signs include pacing, agitated behavior, frequent mood changes and sleeplessness for several nights, actions or threats of assault, physical harm or violence, threats or talk of death or suicide, such as "I don't care anymore," or "You won't need to worry about me much longer," withdrawal from activities and relationships, putting affairs in order, such as saying goodbye to friends, giving away prized possessions or writing a will, a sudden brightening of mood after a period of being depressed, or unusually risky behavior, such as buying or handling a gun or driving recklessly can be indicators of suicidal thinking.

History and physical examination: To diagnosis depression the doctor must first rule out all other disease possibilities. Typically, the diagnosis begins with a medical history, including questions about the duration, severity, and characteristics of symptoms. The physician will ask about diet, stress, any medications currently being taken, and changes in sleep patterns. Questionnaires may be used to determine the level of depression.

Diagnosis also involves ruling out other mental health conditions that may produce symptoms similar to depression. These may include other mood disorders, such as bipolar, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), and borderline personality disorder.

A diagnosis of depressive disorder is based on criteria found in the Diagnostic and Statistical Manual of Mental Disorders-IV-TR (DSM-IV-TR) developed by the American Psychiatric Association.

Laboratory tests: Blood tests can determine if the levels of neurochemicals (brain chemicals), including serotonin, dopamine, and norepinephrine, are healthy. Tests may be ordered to rule out other causes, such as blood or urine tests to determine the balance of salts and sugar in the blood, hormone function, blood cell counts, and drug and alcohol levels. Computerized tomography (CT) scan, positron emission tomography (PET), or magnetic resonance imaging (MRI) of the head may be ordered to check for blood clots, bleeding, or tumors. A spinal tap (lumbar puncture) may be ordered to get a sample of spinal fluid to determine if a brain infection, such as meningitis or encephalitis (both forms of brain inflammation), exists. These tests may rule out other conditions that may be present (such as brain tumor or other disease), and may determine if imbalances in neurochemistry are present.

About half of the people who have a first episode of depression will have another episode within 10 years. The risk of further bouts of depression is higher than in someone who has never been depressed.

Alcohol and drug abuse are very common among people with depression.

Depressive disorder can have devastating effects on relationships as complete isolation and withdrawal during depression are common.

Suicide may be a complication of untreated, mistreated, or misdiagnosed depression. Women attempt suicide more often than men do, but men are much more likely to succeed in killing themselves. The rate of suicide is four times greater for men. Men over 70 are the most likely to commit suicide.

Calling a local suicide hotline, such as the National Suicide Prevention Lifeline at 1-800-273-8255, can be help for someone thinking of suicide.

Treatment for depression usually involves a combination of drug and psychological therapies.

Psychotherapy: Psychotherapy involves talking to a healthcare professional about one's problems and life situation. There are several types of psychotherapy that have been shown to be effective for depression including cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT). Research has shown that mild to moderate depression can often be treated successfully with either of these therapies used alone. However, severe depression appears more likely to respond to a combination of psychotherapy and medication.

Cognitive-behavioral therapy (CBT): CBT helps to change the negative thinking and unsatisfying behavior associated with depression, while teaching individuals how to unlearn the behavioral patterns that contribute to their depression.

Interpersonal therapy (IPT): IPT focuses on improving troubled personal relationships and on adapting to new life roles that may have been associated with a person's depression.

Medications: Drugs used for depression often take two to four weeks to start having an effect, and 6-12 weeks to have their full effect. The first antidepressant medications were introduced in the 1950s. Research has reported that imbalances in neurotransmitters like serotonin, dopamine, and norepinephrine can be improved with antidepressant use.

Selective serotonin reuptake inhibitors (SSRIs):
SSRIs act specifically on the neurotransmitter (brain chemical) serotonin. Serotonin is mainly involved with mood balance. SSRIs are the most common agents prescribed for depression worldwide. These agents increase the amount of serotonin that is available for use by the brain. SSRIs include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), escitalopram (Lexapro®), and fluvoxamine (Luvox®).

Serotonin and norepinephrine reuptake inhibitors (SNRIs):
SNRIs are the second-most popular antidepressants worldwide. These agents increase the amount of both serotonin and norepinephrine. SNRIs include venlafaxine (Effexor®) and duloxetine (Cymbalta®). SSRIs and SNRIs tend to have fewer side effects than other types of antidepressants. Side effects include nausea, nervousness, insomnia, diarrhea, rash, agitation, or sexual side effects (problems with arousal or orgasm).

Norepinephrine-dopamine reuptake inhibitor (NDRI): NDRIs acts by increasing the amounts of dopamine and norepinephrine available to the brain. Bupropion (Wellbutrin®) is commonly used as an antidepressant in this class.

Tricyclic antidepressants (TCAs):
TCAs are older antidepressants that are not used as frequently now. They work similarly to the SNRIs, but have other properties that result in very high side effect rates, as compared to almost all other antidepressants. They are sometimes used in cases where other antidepressants have not worked. TCAs include amitriptyline (Elavil®), desipramine (Norpramin®), doxepin (Sinequan®), imipramine (Norpramin®, Tofranil®), nortriptyline (Pamelor®, Aventyl®), and protriptyline (Vivactil®). TCAs cause side effects that include dry mouth, constipation, bladder problems, sexual problems, blurred vision, dizziness, drowsiness, skin rash, and weight gain or loss.

Monoamine oxidase inhibitors (MAOIs):
MAOs are seldom used now for depression. They also increase amounts of serotonin, norepinephrine, and dopamine for the brain to use in mood stabilization. They can sometimes be effective for people who do not respond to other medications or who have atypical depression with marked anxiety, excessive sleeping, irritability, hypochondria (health anxiety), or phobic (obsessive) characteristics. However, they are the least safe antidepressants to use, as they have important medication interactions, including causing dangerously high blood pressure, and require adherence to a diet free of tyramines, chemicals found in certain foods such as fish (especially dried and salted), chocolate, alcoholic beverages (chianti wine), and fermented foods such as cheese and soy sauce, sauerkraut, and processed meat. MAOIs include phenelzine (Nardil®), isocarboxazid (Marplan®), and tranylcypromine sulfate (Parnate®). A range of other, less serious side effects occur including weight gain, constipation, dry mouth, dizziness, headache, drowsiness, insomnia, and sexual side effects (problems with arousal or satisfaction).

Other:
Mirtazapine (Remeron®) is an antidepressant used commonly in the elderly that helps cause weight gain. A common side effect is drowsiness. Often psychiatrists will combine antidepressants with each other or with agents that are not antidepressants themselves. A class of drugs called atypical antipsychotic agents, including aripiprazole (Abilify®), olanzapine (Zyprexa®), quetiapine (Seroquel®), ziprasidone (Geodon®), and risperidone (Risperdal®) may be used. Side effects for these drugs are high, including excessive sedation and tardive dyskinesia (a nervous system disorder causing facial grimaces, lip smacking, and uncontrollable shaking). According to the American Diabetes Association (ADA), certain antipsychotic drugs may increase the risk of diabetes, obesity and high blood pressure.

Stimulants, such as methylphenidate (Ritalin®) or dextroaphetamine (Dexedrine®) can be added. Stimulants may cause dry mouth, disturbances in sleep patterns, nervousness, anxiousness, and weight loss.

Lithium and mood-stabilizing medications may be prescribed, including lithium (Eskalith®, Lithobid®), valproic acid (Depakene®), divalproex (Depakote®), and carbamazepine (Tegretol®) to treat bipolar depression. Medications called atypical antipsychotics such as olanzapine (Zyprexa), risperidone (Risperdal) and quetiapine (Seroquel) were initially developed for treatment of psychotic disorders.

Hormone therapy: For women with postpartum depression or premenstrual dysphoric disorder (PMDD), hormonal replacement with estrogen and/or progesterone may help with depression. However, there is an increased risk of heart disease and cancer (breast and ovarian) with the use of these medications.

Electroconvulsive therapy:Electroconvulsive therapy (ECT) involves the use of electrical current to stimulate various parts of the brain, and is used mainly in people who have episodes of major depression associated with suicidal tendencies, or in people whose medication has proved to be ineffective. ECT profoundly affects brain metabolism and blood flow to various areas of the brain. How that correlates to easing depression remains unknown, but this therapy is often highly effective. Safety of ECT is controversial, and adverse effects such as confusion, memory loss, headache, hypotension (low blood pressure), and tachycardia (increased heart rate) may occur.

Light therapy: This therapy may help if the individual has seasonal affective disorder (SAD). This disorder involves periods of depression that recur at the same time each year, usually when days are shorter in the fall and winter. Scientists believe fewer hours of sunlight may increase levels of melatonin, a brain hormone thought to induce sleep and depress mood. Treatment in the morning with a specialized type of bright light, which suppresses production of melatonin, may help with this disorder. Melatonin is a hormone for the sleep-wake cycle and may be decreased during depression.

Mild depression: If mild depression is diagnosed, antidepressant drugs are not usually recommended as a first treatment. Exercise seems to help some people with depression. Talking through feelings using counselling may also be helpful for mild depression. Talking to a friend or relative, self-help reading material, or a local self-help group are good choices. If the depression is mild but there is a past history of depression, antidepressants may be used.

Chronic (long term) mild depression or dysthymia (present for two or more years) is more likely in people over 55 years and can be difficult to treat. Individuals diagnosed with dysthymia are usually started on a course of antidepressants.

Moderate depression: If mild depression does not improve, antidepressants or talking treatments are generally used. Research has shown that antidepressants and psychological therapies are equally effective in treating mild or moderate depression but having the two types of treatment together does not seem to offer any extra benefits.

Severe depression: If severe depression is diagnosed, both antidepressant therapy together with psychotherapy are usually used in combination.

Although major depression can be a devastating illness, it is highly treatable. Between 80-90% of individuals diagnosed with major depression can be effectively treated and return to their usual daily activities and feelings.

Hospitalization:
Depression is a serious medical illness. Urgent care and hospitalization may be necessary when someone seems to be a danger to themselves or others, or if they are psychotic. A person experiencing extreme major depression should be brought to the hospital immediately to prevent suicide or possible violence to another person. An acute episode is treated with medications and a low-stimulation environment. Depending on the individual's symptoms and history, longer-term hospitalization may be required.

Light therapy: Light therapy is recommended as a first treatment option for people with seasonal affective disorder (SAD). Fluorescent light box is recommended, but optimal timing and length of light exposure vary between studies.

It is recommended that people use light therapy under the supervision of a qualified professional, rather than attempting to self-medicate. Experts suggest that people wear eye protection when undergoing light therapy. People may need to wear special clothing to protect sensitive areas, such as the genitals, from being burned during light therapy. Light therapy is likely safe when used to treat conditions for which studies or long history of use have shown is safe and effective, such as psoriasis, seasonal affective disorder (SAD), and neonatal jaundice, under a doctor's care. Light therapy is possibly safe when used in combination with a psoralen agent taken by mouth or applied to the skin prior to undergoing psoralen-ultraviolet A (PUVA) phototherapy. Non-targeted phototherapy used alone is possibly safe during pregnancy and breastfeeding. Avoid using PUVA during pregnancy. Avoid taking retinoids by mouth in combination with phototherapy for the treatment of psoriasis in pregnant women. Use cautiously in people with autoimmune disorders, changes in bowel habits, dementia, eating disorders or changes in appetite, headaches or migraines, human immunodeficiency virus (HIV), light sensitivity disorders, muscle pain and weakness, nausea, Parkinson's disease or other movement disorders, psychiatric disorders, risk of dehydration, risk of eye problems, sexual dysfunction, skin cancer, stomach disorders, stomach pain, weak immune systems and in elderly people. Use cautiously in combination with cyclosporine. Combined use may increase the risk of cancer (squamous cell carcinoma), high blood pressure, kidney problems, and liver toxicity. Use cautiously in combination with hydroxychloroquinine, methotrexate, melatonin and with retinoids applied to the skin. Use home phototherapy systems cautiously for the treatment of psoriasis. Medical supervision is recommended. Light therapy may interact with agents that affect the immune system, agents that cause movement problems (extrapyramidal), agents that increase light sensitivity, antibacterials, antibiotics, antidepressants, antiretrovirals, antivirals, depressants, cyclosplorine, hydroxychloroquine, immunoglobulins, khellin, melatonin, metalloporphyrins, methotrexate, phenobarbital, Picrorhiza kurroa, Polypodium leucotomos, retinoids, sedatives, vitamin A, vitamin B12, vitamin C, vitamin D, vitamin D analogs, vitamin E, and other herbs or supplements with similar effects.

Music therapy: Structured music therapy programs have been found to improve mood in institutional long-term care workers facing burnout and autologous stem cell transplant patients. There is also evidence that combining music with guided imagery may lead to reduced fatigue, mood disturbance, and blood levels of cortisol (a stress hormone).

Music therapy is generally known to be safe. Music therapy should generally not be used as the only treatment for serious medical or psychiatric issues.

St. John's wort: St. John's wort has been extensively studied in Europe over the last two decades, with more recent research in the United States. Short-term studies (1-3 months) suggest that St. John's wort is more effective than placebo (sugar pill), and equally effective as tricyclic antidepressants (TCAs) in the treatment of mild-to-moderate major depression. Comparisons to the more commonly prescribed selective serotonin reuptake inhibitor (SSRI) antidepressants, such as fluoxetine (Prozac®) or sertraline (Zoloft®), are more limited. However, other data suggest that St. John's wort may be just as effective as SSRIs with fewer side effects. Safety concerns exist as with most conventional and complementary therapies.

Caution is advised when taking St. John's wort, as numerous adverse effects including many drug interactions are possible. Drug interactions with St. John's wort can have severe consequences. Rare skin reactions, including rash and itching, are reported in human studies. Avoid taking if pregnant or breastfeeding.

Good scientific evidence:

Art therapy: Art therapy enables the expression of inner thoughts or feelings when verbalization is difficult or not possible. It involves the application of a variety of art modalities including drawing, painting, clay and sculpture. Art therapy may be an effective intervention for hospitalized, suicidal adolescents. There is evidence that it can be used to aid in developing a sense of identity and optimism about the future. It may also aid in relaxation and willingness to communicate, and may result in shorter hospitalization.

Art therapy may evoke distressing thoughts or feelings. Use under the guidance of a qualified art therapist or other mental health professional. Some forms of art therapy use potentially harmful materials. Only materials known to be safe should be used. Related clean-up materials (like turpentine or mineral spirits) that release potentially toxic fumes should only be used with good ventilation.

Dehydroepiandoseterone (DHEA): DHEA is a hormone made in the human body that serves as precursor to male and female sex hormones (androgens and estrogens). The majority of clinical trials investigating the effect of DHEA on depression support its use for this purpose under the guidance of a healthcare provider. Further research is needed to confirm these results.

Few side effects are reported when DHEA supplements are taken by mouth in recommended doses. Avoid if allergic to DHEA. Side effects may include fatigue, nasal congestion, headache, acne, or rapid/irregular heartbeats. In women, the most common side effects are abnormal menses, emotional changes, headache, and insomnia. Individuals with a history of abnormal heart rhythms, blood clots or hypercoagulability, and those with a history of liver disease, should avoid DHEA supplements. Patients who are taking antidepressants should avoid DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or anticoagulants (blood thinners), or drugs, herbs, or supplements for diabetes, heart disease, seizure, or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.

Hypnotherapy, hypnosis: Hypnosis appears effective in the treatment of psychosomatic disorders. Additional research is needed to support this finding.

Use cautiously with mental illnesses like psychosis/schizophrenia, manic depression, multiple personality disorder or dissociative disorders. Use cautiously with seizure disorders.

Light therapy: There is conflicting evidence for the use of light therapy in treating nonseasonal depression. Research suggests that light therapy may benefit women who have depression during the menstrual cycle or during pregnancy. However, results are inconclusive.

It is recommended that people use light therapy under the supervision of a qualified professional, rather than attempting to self-medicate. Experts suggest that people wear eye protection when undergoing light therapy. People may need to wear special clothing to protect sensitive areas, such as the genitals, from being burned during light therapy. Light therapy is likely safe when used to treat conditions for which studies or long history of use have shown is safe and effective, such as psoriasis, seasonal affective disorder (SAD), and neonatal jaundice, under a doctor's care. Light therapy is possibly safe when used in combination with a psoralen agent taken by mouth or applied to the skin prior to undergoing psoralen-ultraviolet A (PUVA) phototherapy. Non-targeted phototherapy used alone is possibly safe during pregnancy and breastfeeding. Avoid using PUVA during pregnancy. Avoid taking retinoids by mouth in combination with phototherapy for the treatment of psoriasis in pregnant women. Use cautiously in people with autoimmune disorders, changes in bowel habits, dementia, eating disorders or changes in appetite, headaches or migraines, human immunodeficiency virus (HIV), light sensitivity disorders, muscle pain and weakness, nausea, Parkinson's disease or other movement disorders, psychiatric disorders, risk of dehydration, risk of eye problems, sexual dysfunction, skin cancer, stomach disorders, stomach pain, weak immune systems and in elderly people. Use cautiously in combination with cyclosporine. Combined use may increase the risk of cancer (squamous cell carcinoma), high blood pressure, kidney problems, and liver toxicity. Use cautiously in combination with hydroxychloroquinine, methotrexate, melatonin and with retinoids applied to the skin. Use home phototherapy systems cautiously for the treatment of psoriasis. Medical supervision is recommended. Light therapy may interact with agents that affect the immune system, agents that cause movement problems (extrapyramidal), agents that increase light sensitivity, antibacterials, antibiotics, antidepressants, antiretrovirals, antivirals, depressants, cyclosplorine, hydroxychloroquine, immunoglobulins, khellin, melatonin, metalloporphyrins, methotrexate, phenobarbital, Picrorhiza kurroa, Polypodium leucotomos, retinoids, sedatives, vitamin A, vitamin B12, vitamin C, vitamin D, vitamin D analogs, vitamin E, and other herbs or supplements with similar effects.

Music therapy: There is evidence that music therapy may increase responsiveness to antidepressant medications. In elderly adults with depression, a home-based program of music therapy may have long-lasting effects. In depressed adult women, music therapy may lead to reductions in heart rate, respiratory rate, blood pressure, and depressed mood. Music therapy may also be beneficial in depression following total knee replacement surgery or in patients undergoing hemodialysis.

Music therapy is generally known to be safe. Music therapy should generally not be used as the only treatment for serious medical or psychiatric issues.

Phenylalanine: In early human study, L-phenylalanine, DL-phenylalanine, and D-phenylalanine were shown to reduce symptoms associated with depression. However, high quality clinical trials are needed for better assessment of the antidepressant effectiveness of various forms of phenylalanine dietary supplements.

Use cautiously in patients taking monoamine oxidase inhibitors (MAOIs), or in patients with hypertension, anxiety disorders, psychiatric disorders, or sleep disorders. Avoid in patients with Parkinson's disease or tardive dyskinesia. Avoid in patients with hypersensitivity to phenylalanine or with phenylketonuria (PKU).

Psychotherapy: Psychotherapy is an interactive process between a person and a qualified mental health professional (psychiatrist, psychologist, clinical social worker, licensed counselor, or other trained practitioner). A broad range of psychotherapies have been shown to be effective for the treatment of mild to moderate depression, ante- and postpartum depression, and depression in children. Although prescription medication is the most effective treatment for bipolar disorder, psychotherapy may help patients take their medication, prevent relapses, and reduce suicidal behavior.

Psychotherapy cannot always resolve mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases, symptoms may get worse if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illness or some medical conditions because some forms of psychotherapy may stir up strong emotional feelings and expression. Psychotherapy may help with post-partum depression, but is not a substitute for medication that may be needed in severe cases.

Saffron: Saffron has been suggested as a possible treatment for depression. Crocus petal may also be able to improve symptoms in patients with mild-to-moderate depression. Additional research is needed in this area before a conclusion can be drawn.

Use with caution in those with bleeding disorders, low blood counts, diabetes, low blood sugar, low blood pressure, or in those taking agents for these conditions. Drowsiness may occur; use with caution when driving or operating heavy machinery. Avoid if allergic or sensitive to saffron or any member of the Crocus family. Avoid if pregnant or breastfeeding.

St. John's wort: Early evidence shows that St. John's wort may help with somatoform disorders. Further research is needed to confirm these results.

Caution is advised when taking St. John's wort, as numerous adverse effects including many drug interactions are possible. Drug interactions with St. John's wort can have severe consequences. Rare skin reactions, including rash and itching, are reported in human studies. Avoid taking if pregnant or breastfeeding.

Yoga: Yoga is an ancient system of relaxation, exercise, and healing with origins in Indian philosophy. Several human studies support the use of yoga for depression in both children and adults. Although this preliminary research is promising, better studies are needed.

Yoga is generally considered to be safe in healthy individuals when practiced appropriately. Avoid some inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis, or cervical spondylitis. Certain yoga breathing techniques should be avoided in people with heart or lung disease. Yoga techniques are believed to be safe during pregnancy and breastfeeding when practiced under the guidance of expert instruction (the popular Lamaze techniques are based on yogic breathing). However, poses that put pressure on the uterus, such as abdominal twists, should be avoided in pregnancy.

Unclear or conflicting scientific evidence:

5-hydroxytryptophan (5-HTP): The results of numerous studies in humans suggest that 5-HTP may aid in the treatment of depression. However, it is not known whether 5-HTP is as effective as commonly prescribed antidepressant drugs. In early research, 5-HTP lacked an effect on mood in healthy, young subjects. However, in this population, 5-HTP may impair decision-making. Further well-designed research is needed.

5-HTP should be taken only under the supervision of a qualified healthcare provider. Use cautiously in patients with gastrointestinal disorders, schizophrenia, slow heart rate, HIV/AIDS, or HIV-1 infection; in those with seizure disorders or those using agents that may lower the seizure threshold; in those with a history of mental disorders; in those using CNS antidepressants or decarboxylase inhibitors; and in those taking agents that lower blood pressure. Use caution if driving or operating heavy machinery. Avoid in patients with eosinophilia syndromes, in infants with Down syndrome, in patients with mitochondrial encephalomyopathy, in those with suicidal thoughts, in individuals using "party pills" (benzylpiperazine and trifluoromethylphenylpiperazine), and in patients taking antidepressant medications or any other medications that may affect serotonin levels. Avoid in women who are pregnant or breastfeeding. Avoid with known allergy to 5-HTP-containing products.

Acupressure, shiatsu: Acupressure, or shiatsu, has been used in China for thousands of years for health and healing. Several studies suggest that acupressure therapy may be effective for depression. Further research is needed.

With proper training, acupressure appears to be safe if self-administered or administered by an experienced therapist. No serious long-term complications have been reported, according to scientific data. Hand nerve injury and herpes zoster ("shingles") cases have been reported after shiatsu massage. Forceful acupressure may cause bruising.

Acupuncture: Acupuncture, or the use of needles to manipulate the "chi" or body energy, originated in China over 5,000 years ago. A small number of studies have sought to compare acupuncture with medications used in depression. More studies are needed on this use.

Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders, or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, or neurological disorders. Avoid on areas that have received radiation therapy and during pregnancy. Use cautiously with pulmonary disease (such as asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics, or with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers.

Aromatherapy: Fragrant oils have been used for thousands of years. Aromatherapy is a technique in which essential oils from plants are used with the intention of preventing or treating illness, reducing stress, or enhancing well-being. Preliminary research suggests that lavender (Lavendula officinalis) aromatherapy may be helpful as an adjunct to prescription medications used for depression. Additional research is necessary before a conclusion can be made.

Essential oils should be administered in a carrier oil to avoid toxicity. Avoid with a history of allergic dermatitis. Use cautiously if driving/operating heavy machinery. Avoid consuming essential oils. Avoid direct contact of undiluted oils with mucous membranes. Use cautiously if pregnant.

Ayurveda: Ayurveda, which originated in ancient India over 5,000 years ago, is probably the world's oldest system of natural medicine. Early evidence suggests that a traditional Ayurvedic formula containing extracts of four Indian herbs, Ashvatha, Kapikachu, Dhanvayasa, and Bhuriphali, may have benefits similar to conventional anti-depressant medication. Further studies are needed to confirm the effects of this ayurvedic preparation for mild to moderate depression.

Ayurvedic herbs should be used cautiously because they are potent and some constituents can be potentially toxic if taken in large amounts or for a long time. Some herbs imported from India have been reported to contain high levels of toxic metals. Ayurvedic herbs can interact with other herbs, foods and drugs. A qualified healthcare professional should be consulted before taking.

Bach flower remedies: Depression is one of the major uses of Bach flower remedies. Currently, there is a lack of high-quality clinical trials that have investigated the use of Bach flower remedies for major depressive disorder. Higher quality research is needed in this area. Back flower remedies should not be used in lieu of more proven therapies.

Chasteberry: There is limited evidence suggesting possible benefits of chasteberry in the alleviation of symptoms of pre-menstrual dysphoric disorder (PMDD). Further evidence is necessary before a conclusion can be drawn.

Avoid if allergic or hypersensitive to members of the Vitex (Verbenaceae) family or any chasteberry components. When taken in recommended doses, chasteberry appears to be well tolerated with few side effects. Use cautiously in patients taking oral contraceptives or hormone replacement therapy. Use cautiously with dopamine agonists or antagonists. Avoid with hormone sensitive cancers or conditions (like ovarian cancer or breast cancer). Avoid if pregnant, breastfeeding or if undergoing in vitro fertilization.

Chromium: Early studies show that chromium picolinate may improve symptoms of depression in people with atypical depression. Further research is needed before a recommendation can be made.

Trivalent chromium appears to be safe because side effects are rare or uncommon. However, hexavalent chromium may be poisonous (toxic). Avoid if allergic to chromium, chromate, or leather. Use cautiously with diabetes, liver problems, a weakened immune system (such as HIV/AIDS patients or organ transplant recipients), depression, Parkinson's disease, heart disease, or stroke or in patients who are taking medications for these conditions. Use cautiously if driving or operating machinery. Use cautiously if pregnant or breastfeeding.

Citicholine: According to limited research, citicholine may exert beneficial effects in patients with depression. More well-designed trials are needed before a conclusion can be made.

Use cautiously in patients taking growth hormone or dopaminergic agents. Use cautiously in patients with heart conditions, patients prone to headaches, or in pregnant or lactating patients. Avoid with known allergy or hypersensitivity to citicholine.

Coleus: Limited studies have assessed the efficacy of coleus in the treatment of depression. High quality clinical trials are warranted.

Creatine: Early research suggests a potential beneficial of creatine supplements in depression. Large, well-designed studies are needed.

Avoid if allergic to creatine or with diuretics (like hydrochlorothiazide, furosemide (Lasix®)). Use caution in asthma, diabetes, gout, kidney, liver or muscle problems, stroke or a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding.

Feldenkrais method®: Early research revealed improved mood among participants who enrolled in a one-year program that included the Feldenkrais Method®. There is currently a lack of available scientific studies or reports of safety of the Feldenkrais Method®.

Folate: Folic acid or folate deficiency has been found among many individuals suffering from depression and has been linked to poor response to antidepressant therapies. Folate supplements have been used for enhancing treatment response to antidepressants. Limited clinical research suggests that folic acid is not effective as a replacement for conventional antidepressant therapy. Blood tests can determine if an individual is low in vitamins such as folic acid.

Folate appears to be well tolerated in recommended doses. Avoid if allergic or hypersensitive to folate or any of the product ingredients. It is recommended that pregnant women consume 400 micrograms of folate daily in order to reduce the risk of fetal defects. Folate is likely safe if breastfeeding.

Ginkgo: Preliminary study suggests that ginkgo (Ginkgo biloba) may not be effective for depression and seasonal affective disorder (SAD). Other research in elderly patients with depression shows possible minor benefits. Ginkgo may help in decreasing sexual side effects such as loss of libido in individuals taking antidepressants. Overall, there is not enough evidence to form a clear conclusion. It remains unclear if ginkgo is effective for improving mood in post-menopausal women. Further well-designed research is needed as existing study reports conflicting evidence.

Caution is advised when taking ginkgo supplements as numerous adverse effects and drug interactions are possible. Avoid if allergic or hypersensitive to members of the Ginkgoaceaefamily.
If allergic to mango rind, sumac, poison ivy or oak, or cashews, then allergy to ginkgo is possible. Avoid with blood-thinners (such as aspirin or warfarin) due to an increased risk of bleeding. Ginkgo should be stopped two weeks before surgical procedures. Ginkgo seeds are dangerous and should be avoided. Skin irritation and itching may also occur due to ginkgo allergies. Ginkgo is not recommended during pregnancy or breastfeeding, unless otherwise advised by a doctor.

Guarana: Caffeine, the active ingredient in guarana, may have positive effects on mood enhancement. Caffeine may increase alertness and feelings of well-being and improve performance on sustained attention tasks and simulated driving performance. Slow release caffeine consumption has been correlated with a decrease in calmness and an increase in sleep onset latency.

Avoid if allergic/hypersensitivite to guarana (Paullinia cupana), caffeine, tannins or species of the Sapindaceae family. Avoid with hypertension, psychological or psychiatric disorders, liver impairment, and arrhythmias. Avoid with other stimulatory agents, especially ephedra. Use cautiously with breast disease, impaired kidney function, diabetes, pre-existing mitral valve prolapse, iron deficiency, gastric or duodenal ulcers, bleeding disorders, glaucoma, or if at risk for osteoporosis. Use cautiously if undergoing electroconvulsive therapy (ECT). Avoid if pregnant or breastfeeding.

Healing touch (HT): Preliminary data suggests that a series of healing touch (HT) sessions over time may reduce depression. However, data are insufficient to form definitive conclusions, and studies of better design are needed. HT should not be regarded as a substitute for established medical treatments. Use cautiously if pregnant or breastfeeding.

Hypnotherapy, hypnosis: There is early research that group therapy with hypnosis may prevent depressive episodes, but the data are not conclusive. Further studies are needed in this area.

Use cautiously with mental illnesses like psychosis/schizophrenia, manic depression, multiple personality disorder or dissociative disorders. Use cautiously with seizure disorders.

Kundalini yoga: Kundalini yoga is one of many traditions of yoga that share common roots in ancient Indian philosophy. It is comprehensive in that it combines physical poses with breath control exercises, chanting (mantras), meditations, prayer, visualizations, and guided relaxation. It is an elaborate system focused on healing and "purifying" the mind, body, and emotions. There is preliminary evidence that Kundlini yoga practice may be of benefit in depression. More trials are needed to establish whether this is a viable therapy for depression before a recommendation can be made.

Avoid exercises that involve stoppage of breath with heart or lung problems, insomnia, or with poor memory or concentration. Avoid certain inverted poses with disc disease of the spine, fragile or atherosclerotic neck arteries, risk for blood clots, extremely high or low blood pressure, glaucoma, detachment of the retina, ear problems, severe osteoporosis or cervical spondylitis. Use cautiously with mental disorders as some techniques may cause an altered state of consciousness. Kundalini yoga is considered safe and beneficial for use during pregnancy and lactation when practiced under the guidance of expert instruction. Teachers of yoga are generally not medically qualified and should not be regarded as sources of medical advice for management of clinical conditions.

Lavender: Preliminary research suggests that lavender may be helpful as an adjunct to prescription medications for mild-to-moderate depression. Additional research is necessary before a conclusion can be made.

Avoid if allergic or hypersensitive to lavender. Avoid with history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.

L-carnitine: L-carnitine (also known as acetyl-L-carnitine) is an antioxidant and may help blood flow as well as neurological function. Although the results are promising there is currently insufficient evidence to support the use of acetyl-L-carnitine in the treatment of depression. Well-designed clinical trials with adequate subject number are required.

Caution is advised when taking acetyl-L-carnitine supplements as numerous adverse effects including drug interactions are possible. Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low birth weight infants and individuals on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.

Lemon balm: There is a lack of evidence to show that a combination lemon balm treatment may be effective in treating depression. More research in this area is needed.

Lemon balm is thought to be safe when applied to the skin or taken by mouth in recommended doses (up to 30 days) in otherwise healthy adults and when consumed in amounts normally found in foods. Use cautiously in people with diabetes or low blood sugar or in those taking agents that affect blood sugar. Use cautiously in people with low blood pressure or in those taking agents that lower blood pressure. Use cautiously in people using central nervous system (CNS) depressants, sedatives, or alcohol. Use cautiously in people who have low cholesterol or who are taking cholesterol-lowering agents, including statins. Use cautiously in people who have autoimmune disorders or who are taking agents that may affect immune system function. Use cautiously in people who have glaucoma, heart conditions, thyroid disorders, or in people taking selective serotonin reuptake inhibitors (SSRIs). Avoid in pregnant or breastfeeding women. Avoid with known allergy or sensitivity to lemon balm, any of its parts, or other plants of the Melissa genus.

Massage: Various forms of therapeutic superficial tissue manipulation have been practiced for thousands of years across cultures. Massage is relaxing and may decrease stress. There is currently insufficient evidence to determine if massage is beneficial in patients with depression. Additional research is necessary in order to form a scientifically based recommendation.

Avoid with bleeding disorders, low platelet counts, or if on blood-thinning medications (such as heparin or warfarin). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery or blood clots. Use cautiously if history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

Meditation: There is currently not enough scientific evidence to suggest the effectiveness of meditation for mood enhancement. Some forms of meditation may prevent relapse in patients who have had bouts of major depression. More studies are needed.

Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation, and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies, and should not be used as the sole approach to illnesses.

Melatonin: Melatonin has been suggested for the improvement of sleep disturbances in depression, although research is limited in this area. There are several small, brief studies of melatonin in patients with seasonal affective disorder (SAD). This research is not well designed or reported, and further study is necessary before a clear conclusion can be reached.

Melatonin is not to be used for extended periods of time. Caution is advised when taking melatonin supplements as numerous adverse effects including drug interactions are possible. Melatonin is not recommended during pregnancy or breastfeeding, unless otherwise advised by a doctor. Use cautiously with drugs broken down by the liver, sedative drugs (Ambien®), barbiturates, narcotics, antidepressants, alcohol, drugs that increase the risk of bleeding such as warfarin (Coumadin®), non-steroidal anti-inflammatories (ibuprofen or naproxen), drugs that affect blood pressure (atenolol), drugs that lower levels of vitamin B6 in the body (such as birth control pills, hormone replacement therapy, or loop diuretics), diazepam, verapamil, temazepam, somatostatin, drugs that alter blood sugar levels (insulin), caffeine, succinylcholine, methamphetamine, isoniazid or herbs or supplements with similar effects (such as 5-HTP, Ginkgo biloba,garlic, saw palmetto, vitamin B12, chasteberry, arginine, DHEA, and Echinacea).

Omega-3 fatty acids, fish oil, alpha-linolenic acid:
Essential fatty acids (including omega-3 fatty acids) have many roles in the body, including proper nerve and brain function. There have been several studies on the use of omega-3 fatty acids in depression; however, not enough reliable evidence is available to form a clear conclusion.

Omega-3 fatty acids found in fish oils are normally used. It is important to choose quality fish oil supplements, as heavy metals have been reported in some fish oil supplements. The label should say if the product has been tested for heavy metal contamination (such as lead and mercury). Avoid if allergic or hypersensitive to fish, omega-3 fatty acid products that come from fish, nuts, linolenic acid, or omega-3 fatty acid products that come from nuts. Avoid during active bleeding. Use cautiously with bleeding disorders, diabetes, low blood pressure or drugs, herbs or supplements that treat any such conditions. Use cautiously before surgery. The Environmental Protection Agency (EPA) recommends that intake be limited in pregnant/breastfeeding women to a single six-ounce meal per week, and in young children to less than two ounces per week. For farm-raised, imported, or marine fish, the U.S. Food and Drug Administration (FDA) recommends that pregnant/breastfeeding women and young children avoid eating types with higher levels of methylmercury and less than 12 ounces per week of other fish types. Women who might become pregnant are advised to eat seven ounces or less per week of fish with higher levels of methylmercury or up to 14 ounces per week of fish types with about 0.5 parts per million (such as marlin, orange roughy, red snapper, or fresh tuna).

Prayer, distant healing: Early study suggests that psychiatric inpatients may benefit from anonymous distant healing intention for depression. Additional research is needed.

Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches, and require an open dialog between patients and caregivers.

Psychotherapy: Telephone-administered cognitive-behavioral therapy may help treat depression for multiple sclerosis patients, although more study is needed in this area. Short-term psychotherapy for psychosomatic conditions may not be as effective as long-term psychotherapy. More research needs to be done to evaluate these approaches. Psychotherapy may help seasonal affective disorder (SAD). Further study is needed to confirm early results.

Psychotherapy cannot always resolve mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases, symptoms may get worse if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illness or some medical conditions because some forms of psychotherapy may stir up strong emotional feelings and expression. Psychotherapy may help with post-partum depression, but is not a substitute for medication that may be needed in severe cases.

Reflexology: Reflexology may provide some benefits to patients suffering from depression. However, results from numerous studies have been inconsistent. Further research is needed.

Avoid with recent or healing foot fractures, unhealed wounds, or active gout flares affecting the foot. Use cautiously and seek prior medical consultation with osteoarthritis affecting the foot or ankle, or severe vascular disease of the legs or feet. Use cautiously with diabetes, heart disease or the presence of a pacemaker, unstable blood pressure, cancer, active infections, past episodes of fainting (syncope), mental illness, gallstones, or kidney stones. Use cautiously if pregnant or breastfeeding. Reflexology should not delay diagnosis or treatment with more proven techniques or therapies.

Reiki: Reiki is a Buddhist practice that is approximately 2,500 years old. It is used for stress reduction and relaxation and is administered by "laying on hands" and moving around the "energy" of the body. There is evidence that Reiki may reduce symptoms of depression. Additional research is needed.

Reiki is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Use cautiously with psychiatric illnesses.

Relaxation therapy: Relaxation therapy includes self-control relaxation, paced respiration, and deep breathing. There is promising early evidence from human trials supporting the use of relaxation to reduce symptoms of depression,although effects appear to be short-lived. Better quality research is necessary before a firm conclusion can be drawn.

Avoid with psychiatric disorders such as schizophrenia/psychosis. Jacobson relaxation (flexing specific muscles, holding that position, then relaxing the muscles) should be used cautiously with illnesses like heart disease, high blood pressure, or musculoskeletal injury. Relaxation therapy is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time to diagnosis or treatment with more proven techniques.

Rhodiola: Rhodiola has been used traditionally to reduce depression. In preliminary study of patients with mild-to-moderate depression, the SHR-5 standardized extract of rhodiola decreased symptoms of depression. Further research is needed before conclusions can be made.

Use with caution in patients with diabetes or low blood sugar, and in those taking agents that affect blood sugar. Use with caution in patients with bleeding disorders or in those taking drugs that may increase the risk of bleeding. Use with caution in patients with heart disease or in those taking agents that affect blood pressure or agents that regulate heart rhythm. Use with caution in patients taking sedatives or CNS depressants, immunosuppressants, agents containing piperine (such as black pepper), agents that are processed by the liver's "cytochrome P450" enzyme system, or agents regulated by P-glycoprotein. Avoid in patients using antidepressants. Avoid in patients with known allergy or sensitivity to rhodiola, its constituents, or members of the Crassulaceae family. Avoid in patients who are pregnant or breastfeeding, due to a lack of safety data.

Riboflavin (Vitamin B2): Riboflavin is a water-soluble vitamin, which is involved in many processes in the body, and is necessary for normal cell function, growth, and energy production. Adequate nutrient supplementation with riboflavin may be required for the maintenance of adequate cognitive function. Treatment with B-vitamins, including riboflavin, has been reported to improve depression in patients taking tricyclic antidepressants.

Avoid if allergic or hypersensitive to riboflavin. Since the amount of riboflavin a human can absorb is limited, riboflavin is generally considered safe. Riboflavin is generally regarded as being safe during pregnancy and breastfeeding. The U.S. recommended dietary allowance (RDA) for riboflavin in pregnant women is higher than for non-pregnant women; the RDA during pregnancy is 1.4 milligrams daily, and 1.6 milligrams during breastfeeding.

Sage: Sage is traditionally used to improve mood. Preliminary human study suggests that sage (Salvia lavandulaefolia essential oil or Salvia officinalis leaf as capsules) may aid mood, even in stressful situations. Additional study is needed in this area.

Use cautiously in patients with high blood pressure (hypertension), low blood pressure (hypotension), or in patients taking agents that affect blood pressure. Use cautiously in patients with bleeding disorders or in those taking agents that may increase the risk of bleeding. Use cautiously in patients with diabetes or hypoglycemia or in those taking drugs, herbs, or supplements that affect blood sugar. Use cautiously if driving or operating heavy machinery or if taking certain sedatives or antidepressants. Use the essential oil or tincture of sage cautiously in patients with epilepsy. Only sterile preparations of sage should be used in the eye. Avoid use above dietary levels if pregnant or breastfeeding. Avoid if allergic or hypersensitive to sage species, their constituents, or to members of the Lamiaceae family.

SAMe:
S-adenosylmethionine, or SAMe, is normally formed in the body from the essential amino acid methionine. SAMe supplements are used in depression and mood disorders. SAMe has been studied for use in depression for many decades. However, the majority of trials that have been performed have significant methodological flaws limiting their clinical usefulness. A small number of randomized placebo controlled trials suggest an antidepressant effect that is greater than that observed with placebo. Although some studies have suggested that SAMe has a more rapid onset of action in depression than tricyclic antidepressants (TCAs), it is uncertain whether these effects result in improved patient outcomes. Large randomized placebo controlled trials that compare SAMe to other antidepressants such as Selective Serotonin Reuptake Inhibitors (SSRIs) are needed. Until these trials are available, it is difficult to justify the use of SAMe in patients with depression since there are many effective antidepressants available to this patient population.

Caution should be used when taking SAMe supplements as drug interactions are possible. Avoid if allergic or hypersensitive to SAMe. Use cautiously with diabetes and anxiety disorders, or in women in their third trimester of pregnancy. Avoid with bipolar disorder. Avoid during the first trimester of pregnancy or if breastfeeding.

St. John's wort: There is not enough evidence to determine if St. John's wort is an effective treatment for depression in children younger than 18 years of age. Despite some promising early data, there is currently not enough evidence to recommend St. John's wort for depressive disorder with seasonal pattern or Seasonal Affective Disorder (SAD).

Caution is advised when taking St. John's wort, as numerous adverse effects including many drug interactions are possible. Drug interactions with St. John's wort can have severe consequences. Rare skin reactions, including rash and itching, are reported in human studies. Avoid taking if pregnant or breastfeeding.

Tai Chi: Tai chi is a system of movements and positions believed to have developed in 12th Century China. Tai chi techniques aim to address the body and mind as an interconnected system, and are traditionally believed to have mental and physical health benefits to improve posture, balance, flexibility and strength. Preliminary research suggests that tai chi may help alleviate depression. Patients may experience improved mood as a result of tai chi practice. Additional research is needed.

Avoid with severe osteoporosis or joint problems, acute back pain, sprains, or fractures. Avoid during active infections, right after a meal, or when very tired. Some believe that visualization of energy flow below the waist during menstruation may increase menstrual bleeding. Straining downwards or holding low postures should be avoided during pregnancy, and in patients with inguinal hernias. Some tai chi practitioners believe that practicing for too long or using too much intention may direct the flow of chi (qi) inappropriately, possibly resulting in physical or emotional illness. Tai chi should not be used as a substitute for more proven therapies for potentially serious conditions. Advancing too quickly while practicing tai chi may increase the risk of injury.

Therapeutic touch: Therapeutic touch may offer some benefits when used with standard therapies to treat depression. More research is needed.

Therapeutic touch is believed to be safe for most people. Therapeutic touch should not be used for potentially serious conditions in place of more proven therapies. Avoid with fever or inflammation, and on body areas with cancer.

Valerian: There is currently not enough available scientific evidence on the use of valerian for depression.

Use with caution if allergic to members of the Valerianaceaefamily. Avoid if driving or operating heavy machinery, as it may cause drowsiness. Avoid with liver disease. Avoid if pregnant or breastfeeding.

Vitamin B12: Higher blood levels of homocysteine are associated with increased depression in later life. However, a combination of folic acid, vitamin B12, and vitamin B6 was no better than placebo with respect to symptoms of depression in older men. Well-designed clinical trials are needed to confirm any potential benefit.

Vitamin B12 is generally considered safe when taken in amounts that are not higher than the recommended dietary allowance (RDA). There are not enough scientific data available about the safety of larger amounts of vitamin B12 during pregnancy or breastfeeding. Use cautiously in patients with heart problems (including coronary stenting), elevated blood pressure, skin concerns, genitourinary concerns, gastrointestinal concerns, blood disorders, subnormal serum levels of potassium, gout, or elevated uric acid levels. Use cautiously in patients taking the following agents, as they have been associated with reduced absorption or reduced blood levels of vitamin B12: ACE inhibitors, acetylsalicylic acid (aspirin), antibiotics, anticonvulsants, bile acid sequestrants, colchicine, H2 blockers, metformin, neomycin, nicotine, nitrous oxide, oral contraceptives, para-aminosalicylic acid, potassium chloride, proton pump inhibitors (PPIs), and zidovudine (AZT, Combivir®, Retrovir®). Additionally, vitamin C may cause the degradation of vitamin B12 in multivitamin supplements, and chloramphenicol may inhibit the biosynthesis of vitamin B12. Avoid in patients sensitive or allergic to cobalamin, cobalt, or any other vitamin B12 product ingredients.

Vitamin B6 (Pyridoxine): Some research suggests that pyridoxine supplementation alone or in combination with high doses of other B vitamins may help with depression. Pyridoxine helps increase the "calming" neurochemicals serotonin and gamma amino butyric acid (GABA) levels in the blood, possibly benefiting people in dysphoric mental states. Well-designed clinical trials are needed to confirm potential benefit. Vitamin B6 may be found in a multivitamin or a B-complex vitamin supplement.

Avoid if sensitive or allergic to any vitamin B6 product ingredients. Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). The RDA for pregnant women is 1.9 milligrams per day. For relief of severe nausea in early pregnancy, 30-75 milligrams has been used daily. There is some concern that high-dose pyridoxine taken by a pregnant mother can cause seizures in a newborn. The RDA in breastfeeding women is 2 milligrams per day. Use cautiously if pregnant or breastfeeding.

Vitamin D: Some studies suggest an association between low vitamin D levels in the blood and various mood disorders, including depression, seasonal affective disorder (SAD), and premenstrual syndrome. Also vitamin D supplementation may improve symptoms of depression associated with seasonal affective disorder. Additional research is needed before a conclusion can be made.

Vitamin D is generally well tolerated in recommended doses; doses higher than those recommended may cause toxic effects. Vitamin D is considered safe in pregnant and breastfeeding women when taken in recommended doses. Use cautiously with hyperparathyroidism (overactive parathyroid), diabetes, low blood pressure, kidney disease, liver disease, or granulomatous disorders (a type of immune disorder), or in mothers who are receiving vitamin D supplements and who are breastfeeding. Avoid if allergic or hypersensitive to vitamin D or any of its components or with vitamin D hypersensitivity syndromes. Avoid in patients with hypercalcemia (high blood calcium levels).

Yohimbe: Preliminary clinical study suggests that yohimbine hydrochloride may improve symptoms of depression. However, yohimbe bark extract may not contain significant amounts of yohimbine and therefore may not have antidepressant effects. More research is needed before a firm conclusion can be made.

Yohimbine is generally well tolerated in recommended doses. However, many side effects have been reported with yohimbine hydrochloride and may apply to yohimbe bark. Avoid if allergic to yohimbe, any of its components, or yohimbine-containing products. Use cautiously with peptic ulcer disease, kidney disease, high blood pressure, heart disease or if taking drugs that affect blood sugar levels. Use cautiously in patients with blood disorders or who use blood thinners. Use cautiously in patients with seizure disorders. Use cautiously in patients with asthma or other respiratory disease, insomnia, systemic lupus erythematosus, liver or kidney disease, or a history of kidney failure. Use cautiously in patients using central nervous system (CNS) depressants, alpha blockers, ACE inhibitors, angiotensin II receptor antagonists, beta blockers, calcium channel blockers, diuretics, guanabenz, or guanethidine. Avoid in individuals taking mood stabilizers such as selective serotonin reuptake inhibitors (SSRIs), tricyclic (TCA) antidepressants, or monoamine oxidanse inhibitors (MAOIs). Avoid with benign prostate hypertrophy (enlarged prostate), anxiety, mania, depression, insomnia, stress disorders, post-traumatic stress disorders, bipolar disorders or schizophrenia. Avoid use in children or if pregnant or breastfeeding.

Zinc: Zinc supplementation may improve mood. More well-designed trials are needed before a conclusion may be made.

Zinc is generally considered safe when taken at the recommended dosages. Use amounts regularly exceeding the recommended upper tolerance levels (greater than 40 milligrams daily) under a physician's guidance only. Use cautiously in patients with bleeding disorders, diabetes, or low blood sugar levels, or in patients taking agents for these conditions. Use cautiously in patients with high cholesterol or blood fats, a high risk of developing heart disease, various skin disorders, gastrointestinal disorders, liver disease, genitourinary conditions, blood disorders, neurological disorders, pulmonary or respiratory disorders, immune disorders, or kidney disease, or in patients taking antidepressants, potassium-sparing diuretics, antibiotics (particularly tetracyclines and quinolones), iron, penicillamine, thyroid hormones, or copper. Avoid in patients who are homozygous for hemochromatosis (a metabolic disorder involving the deposition of iron-containing pigments in the tissues and characterized by bronzing of the skin, diabetes, and weakness) or with a known allergy or hypersensitivity to zinc compounds. Avoid use of intranasal Zicam®.

Fair negative scientific evidence:

Psychotherapy: Several studies suggest that patients with psychotic depression are probably not good candidates for psychotherapy and that medication remains the optimal treatment. More research is needed.

Psychotherapy cannot always resolve mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases, symptoms may get worse if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illness or some medical conditions because some forms of psychotherapy may stir up strong emotional feelings and expression. Psychotherapy may help with post-partum depression, but is not a substitute for medication that may be needed in severe cases.

St. John's wort: Studies of St. John's wort for severe depression have not provided clear evidence of effectiveness.

Caution is advised when taking St. John's wort, as numerous adverse effects including many drug interactions are possible. Drug interactions with St. John's wort can have severe consequences. Rare skin reactions, including rash and itching, are reported in human studies. Avoid taking if pregnant or breastfeeding.

Healthcare providers recommend that an individual suffering from depression reduce stress and try to develop regular sleep patterns. Sleep disturbances may signal the early phase of a depressive episode.

Learn to recognize the early warning signs and triggers of depression. Warning signs of relapse vary from patient to patient, and may include thoughts of death, or slight changes in sleep patterns (a common indicator), mood, energy, self-esteem, sexual interest, concentration, and willingness to take on new projects, and dress or grooming.

Major depression: This type of depression lasts more than two weeks. Symptoms may include overwhelming feelings of sadness and grief, loss of interest or pleasure in activities usually enjoyed, and feelings of worthlessness or guilt. This type of depression may result in poor sleep, a change in appetite, severe fatigue and difficulty concentrating. Severe depression may increase the risk of suicide.

Atypical depression: Individuals with atypical depression, as opposed to major depression, experience improved mood when something good happens. In addition, two of the following symptoms occur to have atypical depression: an increase in appetite or weight gain (as opposed to the reduced appetite or weight loss of "typical" depression), excessive sleeping (as opposed to insomnia), leaden paralysis (a severe form of fatigue or tiredness), and sensitivity to rejection.

Dysthymia: Dysthymia is a less severe depression (mild to moderate) than major but a more chronic form of depression. Signs and symptoms usually are not disabling, and periods of mild depression can alternate with short periods of feeling normal. Having dysthymia places an individual at an increased risk of major depression. To be considered having dysthymia, the first two years of depressed mood cannot include any episodes of major depression. In addition, no underlying cause of depressed mood, such as a general medical condition (PMS, menopause, or coronary heart disease) or substance abuse may be present. The symptoms of dysthymia and the associated signs of depression cause significant distress or impairment in social, occupational, and other important areas of functioning. When a major depressive episode occurs on top of dysthymia, healthcare professionals may refer to the resultant condition as double depression.

Adjustment disorders: Having a loved one die, losing a job, or receiving a diagnosis of cancer or another disease can cause an individual to feel tense, sad, overwhelmed, or angry. Eventually, most people come to terms with the lasting consequences of life stresses, but some do not; this is called an adjustment disorder. Adjustment disorders are forms of depression that occur when the response to a stressful event or situation causes signs and symptoms of depression. Some people develop an adjustment disorder in response to a single event such as a parent or spouse dying. In others, it stems from a combination of stressors. Adjustment disorders can be acute (lasting less than six months) or chronic (lasting longer). Doctors classify adjustment disorders based on the primary signs and symptoms of depression.

Bipolar disorder: Having recurrent episodes of depression and elation (mania) is characteristic of bipolar disorder. Because this condition involves emotions at both extremes (poles), it's called bipolar disorder or manic-depressive disorder. Mania affects judgment, causing individuals to make unwise decisions. Some people have bursts of increased creativity and productivity during the manic phase. The number of episodes at either extreme may not be equal. Some people may have several episodes of depression before having another manic phase, or vice versa.

Seasonal affective disorder: Seasonal affective disorder (SAD) is a pattern of depression related to changes in seasons and a lack of exposure to sunlight. SAD usually occurs in winter. It may cause headaches, irritability and a low energy level. SAD is not a chronic (long term) depressive disorder.

Postpartum depression: According to the American College of Obstetricians and Gynecologists, about 10% of new moms experience postpartum depression, a more severe form of depression that can develop within the first six months after giving birth. For women with postpartum depression, feelings such as sadness, anxiety and restlessness can be so strong that they interfere with daily tasks. Rarely, a more extreme form of depression known as postpartum psychosis can develop. Symptoms of this psychosis include a fear of harming oneself or one's baby, confusion and disorientation, hallucinations and delusions, and paranoia.

Premenstrual dysphoric disorder (PMDD): PMDD occurs when depressive symptoms, such as crying, tiredness, and sadness, occur one week prior to menstruation and disappear after menstruation.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.